Label-free, non-destructive, high-resolution metabolic function imaging

Our ultimate goal is to change the paradigm of disease detection through the development of label-free multiphoton microscopes that are ultimately brought to the patient to assess metabolic and micromechanical tissue function non-invasively (or via minimally invasive approaches). We perform studies with two-dimensional cell cultures^1-5, three-dimensional engineered tissues^6-17, C elegans models18, freshly excised tissues^19-21, and living humans^{22, 23}. We have performed studies to develop, establish, and/or validate a number of metabolic function metrics²⁴, including an entirely novel method to characterize mitochondrial networks in vivo in human tissues^{22, 23}. Our studies have been among the first to highlight the unique capabilities of these approaches to assess stem cell differentiation^{2-4, 11}; further, they demonstrated the ability of depth-resolved, label-free assessments of metabolic function to yield a combination of quantitative morphofunctional metrics that lead to superb sensitivity and specificity of detection of high (and low) grade cervical squamous intra-epithelial lesions^{6-10, 21} and skin cancers²². Such metrics have also been used to gain new insights regarding metabolic dysfunction in vitiligo patients and treatment responses^{23, 25}. Bringing the microscope to the patient will not only improve detection, it will enable monitoring of the evolution of diseases, such as pre-cancers, in the same patients and tissue locations over time. This new knowledge will lead to precision diagnostics that can distinguish, for example, pre-cancerous changes that are likely to evolve into lesions that need intervention from ones that regress on their own or patients that are responding to treatment from ones that are not^{23, 25}.